Effect of Single Dose Intranasal Insulin On Cognitive Function

Phase 4

Completed

Conditions: Schizophrenia
Schizoaffective Disorder

Interventions: Drug: Insulin (Humulin)
Drug: Placebo

Registration Number: NCT00646581

Lead Sponsor: University of Massachusetts, Worcester

Brief Summary: The purpose of the study is to find out how a small dose of insulin might affect memory, the ability to concentrate, and improve your daily functioning in patients with schizophrenia and schizoaffective disorders. Insulin is not being used to treat diabetes in this study. The investigators propose a single dose, double-blinded, placebo-controlled trial of intranasal insulin in 40 subjects with schizophrenia or schizoaffective disorder to examine insulin's effect on cognition. The specific aims include:

1. Examine the effects of single doses of 40 IU intranasal insulin compared to placebo on cognitive functioning, including attention and memory.

2. Examine whether single dose of intranasal insulin administration will raise serum insulin level and decrease plasma glucose level

Insulin will be delivered through an air spray pump into your nose. The investigators will be comparing one dose of insulin (40 International Units) with placebo, an inactive liquid.

Detailed Description: Insulin signaling in the brain is associated with improved cognitive function in both animal and human studies. Intranasal administration of insulin, which is non-invasive and minimizes the risk of hypoglycemia, may represent a new intervention approach with the potential to improve cognition and real life functioning in this patient with schizophrenia.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

Inclusion Criteria

Age 18-65 years
Diagnosis of schizophrenia, any subtype or schizoaffective disorder, any subtype
Male or female
Stable dose of the current antipsychotic drug for at least one month
Well established compliance with out-patient treatment per treating clinician's judgement.
Able to complete the cognitive assessment battery (must be English speaking)

Exclusion Criteria

Inability to provide informed consent
Current substance abuse
On clozapine or olanzapine
Psychiatrically unstable per treating clinician's judgement.
Significant medical illnesses including uncontrolled hypertension, diabetes, seizure disorder, severe cardiovascular, cerebrovascular, pulmonary, or thyroid diseases etc.
Incapable to complete the cognitive battery assessment.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Single-Dose Intranasal Insulin	Insulin (Humulin)	Subjects are given a one-time, single dose of intranasal insulin
Placebo (1)	Placebo	Subjects are given a one-time, single dose of placebo intranasal spray

Primary Outcome Measures

Name	Time	Method
Improvement in Cognitive Function- HVLT Immediate Recall Total (Number)	pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration	Subjects performed the HVLT Immediate Recall Task. For this task, participants were read aloud a list of 12 words from three taxonomic categories. Participants were read the list three separate times, and after each reading were immediately asked to recall as many words from the list as they could. The number of words recalled successfully was measured before and after intranasal treatment. Values below represent posttreatment performance minus pretreatment performance.
Improvement in Cognitive Function- HVLT-Delayed Recall (Number)	pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration	Subjects performed the HVLT word recall task after a 20-minute delay before and after intranasal treatment. In the HVLT delayed recall task, participants were asked to recall the same list of 12 words dictated in the immediate recall task 20 minutes after the completion of the immediate recall task. Words successfully recalled after the 20-minute delay were measured. Values below represent posttreatment performance minus pretreatment performance.
CPT d Score	pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration	Subjects performed a computer-based test designed to measure sustained attention (attention to a specific stimuli over a period of several minutes) before and after intranasal treatment. During this test, participants respond as quickly as possible to any consecutive presentation of identical stimuli on the computer screen. The stimuli (2, 3, and 4-digit targets) were presented with increasing cognitive load in successive blocks. Correct responses, responses made to the second of 2 identical stimuli presented in a row, were scored as hits. False alarms were also recorded. The "d prime score" is a score given to each participant on a scale of 0.0- 1.0 in which discrimination sensitivity is measured. A score of zero equates to no sensitivity, whereas a score of 1.0 equates to perfect sensitivity. Values below represent postreatment performance minus pretreatment performance.
Improvement in Cognitive Function- CPT Hits Rate (Proportion)	pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration	Subjects performed a computer-based test designed to measure sustained attention before and after intranasal treatment. The task is described in the previous outcome measure ("CPT d score"). Hits rate refers to each participant's ability to correctly respond to two consecutive target presentations (i.e. correct responses). Hits rate was measured as a proportion of overall attempts (0= no hits, 1.0= 100% accuracy on hits). Values below represent posttreatment performance minus pretreatment performance.
Improvement in Cognitive Function- CPT Reaction Time of Hits (Milliseconds)	pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration	Subjects performed a computer-based test designed to measure sustained attention before and after intranasal treatment. The task is described in detail in a previous outcome measure ("CPT d score"). Reaction time of hits refers to the average time each participant took to correctly respond to a stimuli in milliseconds. Values below represent posttreatment performance minus pretreatment performance.
Improvement in Cognitive Function- CPT False Alarm Rate (Proportion)	pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration	Subjects performed a computer-based test designed to measure sustained attention before and after intranasal treatment. The task is described in detail in a previous outcome measure ("CPT d score"). False alarm rate refers to the proportion of overall attempts that were characterized as incorrect responses (responses to two non-identical targets). Values below represent posttreatment performance minus pretreatment performance.